Low M-r protein tyrosine phosphatase inhibits growth and migration of vascular smooth muscle cells induced by platelet-derived growth factor

Vascular smooth muscle cell (VSMC) migration and growth are positively regu lated by protein tyrosine phosphorylation. Therefore, a dephosphorylation p rocess controlled by protein tyrosine phosphatases (PTPs) must also be crit ical. The present study identified six cytoplasmic PTPs expressed in VSMCs: low M-r protein tyrosine phosphatase (LMW-PTP), SHP-2, PTP36, PTP2, PTP1B, and FAP1. We further examined the functions of LMW-PTP in VSMCs using the adenovirus-mediated gene transfer of recombinant LMW-PTP. PDGF-induced acti vation of p38, but not of ERK MAP kinase, was blocked by LMW-PTP. LMW-PTP a s well as the p38 inhibitor SB203580 inhibited DNA synthesis and cell migra tion upon PDGF stimulation. LMW-PTP dephosphorylated activated PDGF recepto rs in NIH3T3 cells, but not in VSMCs. Thus, LMW-PTP negatively regulates PD GF functions by inhibiting the p38 pathway in VSMCs although its substrate is unclear. These findings strongly demonstrate that PTPs are important as negative regulators for VSMC growth and migration, processes that are close ly related to the progression of atherosclerosis. (C) 2001 Elsevier Science .